Field of the Invention
The present invention relates generally to field of pharmacotherapy of asthma. More specifically, the present invention discloses a method of co-administering beta-adrenergic antagonists with inverse agonist activity and corticosteroids allowing for a significant reduction of steroid levels without any loss in the anti-inflammatory ability.
Description of the Related Art
Asthma is a common chronic inflammatory disease of the airways characterized airway hyper responsiveness, by reversible airflow obstruction and poorly reversible airway remodeling (1). A distinguishing feature of asthma is airway infiltration by inflammatory cells such as TH2 lymphocytes and eosinophils (2), generating a broad range of inflammatory mediators. One consequence of this inflammation is changes to the surface epithelium of intrapulmonary airways, which acquire a mucus producing, goblet cell phenotype (1, 3-5). Glucocorticosteroids are the most effective treatment available for the long term management of asthma (6-7). These drugs reduce asthma symptoms (6-7), reduce the risk of asthma exacerbations (8), and improve the quality of life (9-10). In addition, glucocorticosteroids reduce inflammation (7, 11-12) and mucous metaplasia (13-14).
Despite their proven efficacy in persistent asthma, enthusiasm for glucocorticosteroid use is tempered by concern about their adverse effects. These adverse effects, such as cataracts have been shown to be positively correlated with the dose of inhaled glucocorticosteroids (15-17). Indeed, in some patients long-term use of high doses of inhaled glucocorticosteroids can produce a similar side effect profile to that of oral steroid use, including reduction in growth velocity, cataracts, glaucoma, osteoporosis, and fractures (18).
Therefore, the availability of additional effective anti-inflammatory agents that could lower the required dose of glucocorticosteroids would be advantageous. Such compounds have been termed ‘steroid-sparing’, implying that concomitant use will allow lower doses of steroid to be used without any loss of therapeutic efficacy. In an allergen-driven murine model of asthma, chronic administration of β-blockers, specifically β2-adrenoceptor (β2-AR) with inverse agonist activity, attenuated mucous metaplasia, airway hyperresponsiveness and inflammation (19-20). Furthermore, one of these β-blockers decreased airway hyperresponsiveness in mild asthmatics (21-22).
The prior art is deficient in steroid-sparing therapeutic regimens for the treatment of asthma. The present invention fulfills this longstanding need and desire in the art.